Background

Leprosy is a chronic infection caused by the acid-fast, rod-shaped bacillus Mycobacterium leprae. Leprosy can be considered 2 connected diseases that primarily affect superficial tissues, especially the skin and peripheral nerves. Initially, a mycobacterial infection causes a wide array of cellular immune responses. These immunologic events then elicit the second part of the disease, a peripheral neuropathy with potentially long-term consequences.

The social and psychological effects of leprosy, as well as its highly visible debilities and sequelae (as seen in the image below), have resulted in a historical stigma associated with leprosy. To minimize the prejudice against those with leprosy, the condition is also known as Hansen disease, named after G.A. Hansen, who is credited with the 1873 discovery of M leprae. This mycobacterium grows extremely slowly and has not been successfully cultured in vitro.

In the 1990s, the World Health Organization (WHO) launched a campaign to eliminate leprosy as a public health problem by 2000. Elimination, as defined by the WHO, was defined as a reduction of patients with leprosy requiring multidrug therapy to fewer than 1 per 10,000 population. This goal was achieved in terms of global prevalence by 2002. As of 2014, none of the 122 countries where leprosy was endemic in 1985 still have prevalence rates of greater than 1 per 10,000 population.
[1]

Although multidrug regimens had been used globally to cure nearly 14 million patients with leprosy since 1985, the number of new leprosy cases remained relatively unchanged from 1980 to 2000, ranging from 500,000-700,000 worldwide per year.
[2] Between 2001 and 2006, the global incidence of leprosy declined suddenly, largely owing to new case reductions in India. There is debate as to whether this decline in India reflects genuine progress against the disease or an interruption of active case detection.
[3]

The goal of the WHO by the end of 2015 is to reduce the rate of new cases with grade-2 disabilities worldwide by at least 35%. This will be carried out by enforcing activities to decrease the delay in diagnosing the disease and actuate treatment with multidrug therapy. This will also have the impact of reducing transmission of the disease in the community.
[2] The results of this effort have yet to be published.

Access and delivery of antibiotics continues to be a problem in the most endemic nations. With the precise transmission mechanism of leprosy still unknown and lack of an effective vaccine, leprosy will probably continue to pose an ongoing public health problem in the coming decades.

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Pathophysiology

Leprosy can manifest in different forms, depending on the host response to the organism.

Individuals who have a vigorous cellular immune response to M leprae have the tuberculoid form of the disease that usually involves the skin and peripheral nerves. The number of skin lesions is limited, and they tend to be dry and hypoesthetic. Nerve involvement is usually asymmetric. This form of the disease is also referred to as paucibacillary leprosy because of the low number of bacteria in the skin lesions (ie, < 5 skin lesions, with absence of organisms on smear). Results of skin tests with antigen from killed organisms are positive in these individuals.

Individuals with minimal cellular immune response have the lepromatous form of the disease, which is characterized by extensive skin involvement. Skin lesions are often described as infiltrated nodules and plaques, and nerve involvement tends to be symmetric in distribution. The organism grows best at 27-30°C; therefore, skin lesions tend to develop in the cooler areas of the body, with sparing of the groin, axilla, and scalp. This form of the disease is also referred to as multibacillary leprosy because of the large number of bacteria found in the lesions (ie, >6 lesions, with possible visualization of bacilli on smear). Results of skin tests with antigen from killed organisms are nonreactive.

Patients may also present with features of both categories; however, over time, they usually evolve to one or the other (indeterminate or borderline leprosy). Interestingly, most individuals who are exposed to leprosy never develop the disease.

Classification of leprosy

Leprosy has 2 classification schemas: the 5-category Ridley-Jopling system and the simpler and more commonly used WHO standard.
[4]

Ridley-Jopling: Depending on the host response to the organism, leprosy can manifest clinically along a spectrum bounded by the tuberculoid and lepromatous forms of the disease. Most patients fall into the intermediate classifications, which include borderline tuberculoid leprosy, midborderline leprosy, and borderline lepromatous leprosy. The classification of the disease typically changes as it evolves during its progression or management. The Ridley-Jopling system is used globally and forms the basis of clinical studies of leprosy. It may also be more useful in guiding treatment regimens and assessing risk of acute complications. Physical findings in each subtype are presented in the Clinical section.

​According to the WHO, in an endemic area, an individual is considered to have leprosy if he or she shows either of the two following signs:
[4]

A skin lesion consistent with leprosy and definite sensory loss, with or without thickened nerves

Positive skin smears

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Epidemiology

Frequency

United States

In 2014, according to the U.S. Department of Health and Human Services, 175 new cases of leprosy were detected in the United States.
[5]

Eighty-five percent of leprosy cases in the United States are found in immigrants,
[6] although endemic foci exist in parts of Louisiana, Florida, and Texas along the Gulf of Mexico; in Mexican and Asian California populations; and in Spanish Americans in New York City.

Some cases among native US citizens can be accounted for by exposure to leprosy overseas. Some cases can be attributed to a contact with a known case of leprosy or exposure to infected armadillos.

Based on genetic analysis studies, wild armadillos and many patients with leprosy in the southern United States are infected with the same strain of M leprae.
[7] Leprosy may be a zoonosis in the southern United States because armadillos are a large reservoir for this disease.

Nonetheless, history of exposure cannot be verified in many patients.
[8]

International

According to WHO figures and as reported by 130 countries, the global annual detection rates have declined from 2004-2010, when 407,791 and 228,474 new cases were reported, respectively (see the images below). The prevalence registered worldwide at the beginning of 2010 was 192,246 cases. Of the new cases, 95% were detected worldwide during 2010 in the following countries: Angola, Bangladesh, Brazil, China, Democratic Republic of the Congo, India, Ethiopia, Indonesia, Madagascar, Mozambique, Myanmar, Nepal, Nigeria, Philippines, Sri Lanka, Sudan, and United Republic of Tanzania.
[2] These countries still exhibit pockets of high endemicity.

Leprosy is rarely fatal, and the primary consequence of infection is nerve impairment and debilitating sequelae. According to one study, 33-56% of newly diagnosed patients already displayed signs of impaired nerve function.
[9] According to estimates, 3 million people who have completed multidrug therapy for leprosy have sustained disability due to nerve damage. Although both lepromatous leprosy and tuberculoid leprosy involve the skin and peripheral nerves, tuberculoid leprosy has more severe manifestations. Nerve involvement results in loss of sensory and motor function, which may lead to frequent trauma and amputation. The ulnar nerve is most commonly involved.

Damage in the following nerves is associated with characteristic impairments in leprosy:

Infiltration by bacteria may lead to destruction of nasal cartilage (lepromatous leprosy), ocular involvement, and diffuse thickening of the skin. Advanced cases of leprosy involve the loss of eyebrows and lashes, but these deformities are less common today.

Worldwide, leprosy is considered the most common cause of crippling of the hand, which is caused by ulnar nerve involvement.
[10] Peroneal nerve involvement can lead to foot drop, posterior tibial nerve involvement, and clawed toes.

Race

Leprosy was once endemic worldwide, and no racial predilection is known. In the late 1800s, the incidence of leprosy in northern Europe and North America dropped dramatically, and the disease is now reported primarily in tropical areas.

Sex

Leprosy is generally more common in males than in females, with a male-to-female ratio of 2:1. In some areas in Africa, the prevalence of leprosy among females is equal to or greater than that in males.
[11]

Age

Leprosy can occur at any age, but, in developing countries, the age-specific incidence of leprosy peaks in children younger than 10 years, who account for 20% of leprosy cases. Leprosy is very rare in infants; however, they are at a relatively high risk of acquiring leprosy from the mother, especially in cases of lepromatous leprosy or midborderline leprosy.

U.S. Department of Health and Human Services. National Hansen's Disease (Leprosy) Program. Health Resources and Services Administration. Available at http://www.hrsa.gov/hansensdisease/. Accessed: March 23, 2016.

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London